FINDINGS: In the comparison of immediate versus deferred
zidovudine, during a median follow-up of 50 months, 1908 individuals progressed, of whom 1351 died. In the deferred group, 61% started antiretroviral
therapy (median time to
therapy 28 months, which was
zidovudine monotherapy in 94%). During the first year of follow-up, immediate
zidovudine halved the rate of
disease progression (p<0.0001), increasing the probability of
AIDS-free survival at 1 year from 96% to 98%. This early delay did not persist: after 6 years,
AIDS-free survival was 54% in both groups. At no time was there any difference in overall survival, which at 6 years was 64% with immediate and 65% with deferred
zidovudine (rate ratio 1.04 [95% CI 0.94-1.15]). In the comparison of
zidovudine plus
didanosine or
zalcitabine versus
zidovudine alone, during a median follow-up of 29 months, 2904 individuals progressed, of whom 1850 died. The addition of
didanosine to
zidovudine delayed both progression (rate ratio 0.74 [0.67-0.82], p<0.0001) and death (0.72 [0.64-0.82], p<0.0001). Similarly, the addition of
zalcitabine to
zidovudine also delayed progression (0.86 [0.78-0.94], p=0.001) and death (0.87 [0.77-0.98], p=0.02). After 3 years, the estimated percentages alive and without a new
AIDS event were 53% for
zidovudine plus
didanosine, 49% for
zidovudine plus
zalcitabine, and 44% for
zidovudine alone; the percentages alive were 68%, 63%, and 59%, respectively. Five of the six trials involved randomised comparisons of
zidovudine plus
didanosine versus
zidovudine plus
zalcitabine: in these, the
zidovudine plus
didanosine regimen had greater effects on
disease progression (p=0.004) and death (p=0.009).
INTERPRETATION: